Catalytic triad

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Catalytic triad refers to three amino acid residues found inside the active site of certain proteases; serine, aspartate (aspartic acid) and histidine. They work together to break peptide bonds on polypeptides. An example of this structure is present in chymotrypsin, where the triad consists of S195, H57 and D102. Essentially, S195 holds onto the polypeptide at the cleavage site; the c-terminal side of F, W or Y, while the bond is hydrolyzed. The mechanism for this reaction is outlined below:

Upon binding of the target protein, the carboxylic group (-COOH) on D102 forms a low-barrier hydrogen bond with H57, increasing the pKa of its imidazole nitrogen from 7 to about 12. This allows H57 to act as a powerful general base, and deprotonate S195.

The deprotonated S195 serves as a nucleophile, attacking the alpha carbon on the c-terminal side of an F, Y or W residue and forcing the carbonyl oxygen to accept an electron, and transforming the alpha carbon into a tetrahedral intermediate. This intermediate is stabilized by an oxanion hole, which also involves S195.

Collapse of this intermediate back to a carbonyl causes H57 to donate its proton to the nitrogen attached to the alpha carbon. The nitrogen and the attached peptide fragment (c-terminal to the F W or Y residue) leave by diffusion.

A water molecule then donates a proton to H57 and the remaining OH- attacks the alpha carbon, forming another tetrahedral intermediate. The OH isn't as nice of leaving group as the c-terminal fragment was, so when the tetrahedral intermediate collapses again, S195 detaches from the a-carbon, taking a proton back from H57.